Prehabilitation in major abdominal surgery:risk stratification and optimising perioperative care

With the aging of the population, the incidence of abdominal tumours is also increasing. Surgery is an important treatment modality for such tumours. However, surgery is still associated with 20-30% risk of perioperative complications. This is due to several reasons. The patient's condition is an important risk factor for the development of complications. The preoperative optimisation of the patient's condition, in preparation for treatment, is called prehabilitation. There is increasing interest in prehabilitation, although it is not yet standard care. This is partly because there are still some remaining questions such as: what is the optimal training program, for whom prehabilitation is (most) suitable or necessary and whether it is cost effective. This manuscript describes studies that address these issues. One study shows that preoperative partially supervised home training has high effectiveness in improving aerobic fitness, in patients scheduled for liver or pancreas surgery for cancer. In addition to physical fitness, however, a prehabilitation program must also address other "modifiable" risk factors such as malnutrition, anaemia (due to iron deficiency), frailty, substance use (smoking/alcohol), and impaired psychological resilience (anxiety/stress). Another study shows that a prehabilitation program targeting these six factors is also estimated to have financial benefits in patients undergoing pancreatic surgery. Prehabilitation gives the most benefit in high-risk patients. Therefore, it is important to make an adequate risk stratification for each patient. Furthermore, this thesis discusses muscle loss after surgery. To improve postoperative outcomes in major abdominal surgery, muscle loss after surgery should be prevented

Low health literacy is associated with worse postoperative outcomes following hepato-pancreato-biliary cancer surgery

Background: Low health literacy (HL) can lead to worse health outcomes for patients with chronic diseases and could also lead to worse postoperative outcomes. This retrospective cohort study investigates the association between HL and postoperative textbook outcome (TO) after hepato-pancreato-biliary (HPB) cancer surgery. Methods: Patients that consented and underwent surgery for a premalignant andmalignant HPB tumor were included. Preoperatively, HL was measured by the brief health literacy screen (BHLS). Patients were categorized as having low or adequate HL. Primary outcome was TO (length of hospital stay (LOS) ≤ 75th percentile; and no severe complication; and no readmission and mortality within 30 days after discharge). Secondary outcomes were LOS and emergency department (ED) visits within 30 days after discharge. Results: In total, 137 patients were included, of whom thirty-six patients had low HL. In patients with low HL (vs. adequate HL), rate of TO was lower (55.6% vs. 72.3%; p = 0.095), LOS was significantly longer (13.5 vs. 9 days; p = 0.007) and there was only a slight difference in ED visits (14.3% vs. 11.0%; p = 0.560). Patients with low HL had a significant lower chance of achieving TO (OR 0.400, 95%-CI 0.169–0.948; p = 0.037). Conclusion: Low HL leads to worse postoperative outcome after HPB cancer surgery. Better preoperative education and guidance of patients with low HL could lead to better postoperative outcomes. Therefore, HL could be the next modifiable risk factor before major surgery

The ultimate preoperative C-reactive protein-to-albumin ratio is a prognostic factor for survival after pancreatic cancer resection

Background: Emerging evidence indicates that an elevated C-reactive protein-to-albumin ratio (CAR) may be associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Further evidence showing that this ratio has significant prognostic value could contribute to current prediction models and clinical decision-making. Methods: Data were analysed of consecutive patients who underwent curative pancreatic resection between 2013 and 2018 and were histologically diagnosed with PDAC. We investigated the relation between the ultimate preoperative CAR and overall survival. Results: A total of 163 patients were analysed. Median overall survival was 18 months (IQR 9-36). Multivariate analysis demonstrated that a higher CAR (HR 1.745, P = 0.004), a higher age (HR 1.062, P < 0.001), male sex (HR 1.977, P = 0.001), poor differentiation grade (HR 2.812, P < 0.001), and positive para-aortic lymph node(s) (HR 4.489, P < 0.001) were associated with a lower overall survival. Furthermore, a CAR ≥ 0.2 was associated with decreased overall survival (16 vs. 26 months, P = 0.003). Conclusion: We demonstrated that an ultimate preoperative elevated CAR is an independent indicator of decreased overall survival after resection for PDAC. The preoperative CAR may be of additional value to the current prediction models

A prospective cohort study evaluating screening and assessment of six modifiable risk factors in HPB cancer patients and compliance to recommended prehabilitation interventions

INTRODUCTION: Despite improvements in perioperative care, major abdominal surgery continues to be associated with significant perioperative morbidity. Accurate preoperative risk stratification and optimisation (prehabilitation) are necessary to reduce perioperative morbidity. This study evaluated the screening and assessment of modifiable risk factors amendable for prehabilitation interventions and measured the patient compliance rate with recommended interventions.METHOD: Between May 2019 and January 2020, patients referred to our hospital for HPB surgery were screened and assessed on six modifiable preoperative risk factors. The risk factors and screening tools used, with cutoff values, included (i) low physical fitness (a 6-min walk test &lt; 82% of patient's calculated norm and/or patient's activity level not meeting the global recommendations on physical activity for health). Patients who were unfit based on the screening were assessed with a cardiopulmonary exercise test (anaerobic threshold ≤ 11 mL/kg/min); (ii) malnutrition (patient-generated subjective global assessment ≥ 4); (iii) iron-deficiency anaemia (haemoglobin &lt; 12 g/dL for women, &lt; 13 g/dL for men and transferrin saturation ≤ 20%); (iv) frailty (Groningen frailty indicator/Robinson frailty score ≥ 4); (v) substance use (smoking and alcohol use of &gt; 5 units per week) and (vi) low psychological resilience (Hospital Anxiety and Depression Scale ≥ 8). Patients had a consultation with the surgeon on the same day as their screening. High-risk patients were referred for necessary interventions.RESULTS: One hundred consecutive patients were screened at our prehabilitation outpatient clinic. The prevalence of high-risk patients per risk factor was 64% for low physical fitness, 42% for malnutrition, 32% for anaemia (in 47% due to iron deficiency), 22% for frailty, 12% for smoking, 18% for alcohol use and 21% for low psychological resilience. Of the 77 patients who were eventually scheduled for surgery, 53 (68.8%) needed at least one intervention, of whom 28 (52.8%) complied with 100% of the necessary interventions. The median (IQR) number of interventions needed in the 77 patients was 1.0 (0-2).CONCLUSION: It is feasible to screen and assess all patients referred for HPB cancer surgery for six modifiable risk factors. Most of the patients had at least one risk factor that could be optimised. However, compliance with the suggested interventions remains challenging.</p

Behavioral genetics of temperament and frontal asymmetry in early childhood

Temperament has been suggested to be influenced by genetic and environmental factors. The current study examined genetic shared environmental and unique environmental factors accounting for variation in Fear, Effortful Control (EC), and Frontal Asymmetry (FA) in 4- to 6-year-old children using bivariate behavioral genetic modeling. We included a total of 214 same-sex twin pairs: 127 monozygotic (MZ) and 87 dizygotic (DZ) pairs. FA was measured during a rest electroencephalogram (EEG) recording, and Fear and EC were measured using parent report. Results show that differences between twins were best explained by genetic factors (about a quarter of the variance) and unique environmental factors (about three quarters of the variance). However, the cross-trait, within-twin correlations were not significant, implying no overlapping genetic or environmental factors on Fear and EC or on Fear and FA. Future research should try to elucidate the large role of unique environmental factors in explaining variance in these temperament-related traits

The association between preoperative body composition and aerobic fitness in patients scheduled for colorectal surgery

AIM: Although cardiopulmonary exercise testing (CPET) is considered the gold standard, a preoperative abdominal CT scan might also provide information concerning preoperative aerobic fitness for risk assessment. This study aimed to investigate the association between preoperative CT‐scan‐derived body composition variables and preoperative CPET variables of aerobic fitness in colorectal surgery. METHOD: In this retrospective cohort study, CT images at level L3 were analysed for skeletal muscle mass, skeletal muscle radiation attenuation, visceral adipose tissue (VAT) mass and subcutaneous adipose tissue mass. Regression analyses were performed to investigate the relation between CT‐scan‐derived body composition variables, CPET‐derived aerobic fitness and other preoperative patient‐related variables. Logistic regression analysis was performed to predict a preoperative anaerobic threshold (AT) ≤ 11.1 ml/kg/min as cut‐off for having a high risk for postoperative complications. RESULTS: Data from 78 patients (45 men; mean [SD] age 74.5 [6.4 years]) were analysed. A correlation coefficient of 0.55 was observed between absolute AT and skeletal muscle mass index. Absolute AT (R (2) of 51.1%) was lower in patients with a lower skeletal muscle mass index, together with higher age, lower body mass and higher American Society of Anesthesiologists (ASA) score. Higher ASA score (odds ratio 5.64; P = 0.033) and higher VAT mass (odds ratio 1.02; P = 0.036) were associated with an increased risk of an AT ≤ 11.1 ml/kg/min. CONCLUSION: Body composition variables from the preoperative CT scan were moderately associated with preoperative CPET‐derived aerobic fitness. Higher ASA score and higher VAT mass were associated with an increased risk of an AT ≤ 11.1 ml/kg/min

Transcriptional analysis of the response of \u3ci\u3eC. elegans\u3c/i\u3e to ethanol exposure

Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses of Caenorhabditis elegans across a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source

ATF4 links ER stress with reticulophagy in glioblastoma cells

Selective degradation of the endoplasmic reticulum (ER; reticulophagy) is a type of autophagy involved in the removal of ER fragments. So far, amino acid starvation as well as ER stress have been described as inducers of reticulophagy, which in turn restores cellular energy levels and ER homeostasis. Here, we explored the autophagy-inducing mechanisms that underlie the autophagic cell death (ACD)-triggering compound loperamide (LOP) in glioblastoma cells. Interestingly, LOP triggers upregulation of the transcription factor ATF4, which is accompanied by the induction of additional ER stress markers. Notably, knockout of ATF4 significantly attenuated LOP-induced autophagy and ACD. Functionally, LOP also specifically induces the engulfment of large ER fragments within autophagosomes and lysosomes as determined by electron and fluorescence microscopy. LOP-induced reticulophagy and cell death are predominantly mediated through the reticulophagy receptor RETREG1/FAM134B and, to a lesser extent, TEX264, confirming that reticulophagy receptors can promote ACD. Strikingly, apart from triggering LOP-induced autophagy and ACD, ATF4 is also required for LOP-induced reticulophagy. These observations highlight a key role for ATF4, RETREG1 and TEX264 in response to LOP-induced ER stress, reticulophagy and ACD, and establish a novel mechanistic link between ER stress and reticulophagy, with possible implications for additional models of drug-induced ER stress

Program for climate-smart livestock systems. Country stocktake: Kenya

This is one of a series of documents that summarises information relating to the livestock sector in the three PCSL countries (Ethiopia, Kenya and Uganda). Prevailing livestock systems and their baseline performance in Kenya are summarised first, followed by a summary of what is known about the impacts of climate change on livestock production and livestock systems. Section 4 briefly summarises some recent research on adaptation and mitigation options for livestock systems in Kenya. Section 5 considers some of the work that has been done to date on projections for the livestock sector to the middle of the century. Section 6 considers the national livestock and climate change policy environment. The paper concludes with a consideration of system intervention points and major gaps in knowledge, to help guide project activities in Kenya

Program for climate-smart livestock systems. Country stocktake: Ethiopia

This is one of a series of documents that summarises information relating to the livestock sector in the three PCSL countries (Ethiopia, Kenya and Uganda). Prevailing livestock systems and their baseline performance in Ethiopia is summarised first, followed by a summary of what is known about the impacts of climate change on livestock production and livestock systems. Section 4 briefly summarises some recent research on adaptation and mitigation options for livestock systems in Ethiopia. Section 5 considers some of the work that has been done to date on projections for the livestock sector to the middle of the century. Section 6 considers the national livestock and climate change policy environment. The paper concludes with a consideration of system intervention points and major gaps in knowledge, to help guide project activities in Ethiopia